Abstract: 【Objective】 This study aimed to investigate the genetic diversity of different buffalo populations and determine the genetic relationships among breeds， so as to provide a theoretical basis for subsequent research on the conservation， breeding， and formation mechanisms of distinctive traits in Guangxi buffaloes. 【Method】 Jugular vein blood samples were collected from buffalo breeds Murrah， Nili-Ravi， and a hybrid （F₁ hybrid of Murrah and Guangxi buffaloes）. Simplified genome sequencing was performed using the Illumina HiSeq^TM 2000 platform. Principal component analysis （PCA） and pedigree analysis revealed that the genetic relationships and population structure among different buffalo populations. Linkage disequilibrium decay and the fixed coefficient （F_ST） between populations were calculated to identify selective genes associated with economic traits of buffalo. KEGG signaling pathway enrichment analysis was conducted for these genes using the DAVID v6.8 database. 【Result】 The average alignment rate of the effective sequences （clean reads） obtained from the simplified genome sequencing of the three buffalo populations to the buffalo 4^th version of reference genome （GCA_003121395.1） was 99.54%. After SNP quality control and filtering， 2012270 SNPs were obtained. A significant genetic difference was found between Murrah and Nili-Ravi buffaloes， with considerable genetic distance between individuals within the populations， indicating a distant relationship； compared to the hybrids with Nili-Ravi buffaloes， the hybrids with Murrah buffaloes were genetically closer （F_ST values all less than 0.40）. A total of 31 shared selective genes were identified among the three buffalo populations， and they were mainly enriched in synaptic membrane and protein phosphorylation pathways， involving five genes： AMPA glutamate receptor subunit α-1 （GRIA1）， potassium calcium-activated channel subfamily Mα-1 （KCNMA1）， Abelson murine leukemia viral oncogene homolog 1 （ABR）， TRIO Rho guanine nucleotide exchange factor （TRIO）， and mitogen-activated protein kinase kinase kinase kinase 4 （MAP4K4）. 【Conclusion】 Through simplified genome resequencing， 31 candidate genes potentially associated with economic traits of buffalo are identified from Murrah， Nili-Ravi， and hybrid buffalo populations. These genes are mainly enriched in synaptic membrane and protein phosphorylation pathways. Among them， GRIA1， KCNMA1， ABR， TRIO， and MAP4K4 play important roles in neural regulation and hormonal regulation， indirectly influencing buffalo body size， reproduction， and lactation performance through biological processes such as the nervous system， immune response， and cell behavior.